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Safety and Effectiveness of Raltegravir Plus Darunavir/Ritonavir in Treatment-Naive HIV-Infected Adults

11 de octubre de 2018 actualizado por: AIDS Clinical Trials Group

A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects

The purpose of this study is to assess the effectiveness and safety of an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

Despite the remarkable strides made in the treatment of HIV-1-infected persons over the last decade, current first-line ART regimens are imperfect. The ideal combination, unlike some current first-line options, would have uncompromised efficacy in the presence of transmitted drug-resistant variants. The primary purpose of this study is to estimate the cumulative proportion of ART-naive participants experiencing virologic failure at or prior to week 24 after initiating raltegravir (RAL) plus darunavir/ritonavir (DRV/RTV).

The study will last 52 weeks. All participants will follow the same treatment schedule and take RAL plus DRV/RTV orally daily for the duration of the trial.

After entry, all participants will have scheduled visits at weeks 1, 4, 12, 24, 36, 48, and 52. Medical/medication history, blood and urine collection, and liver function tests will occur at screening. A targeted physical exam and concomitant medications history will occur at all study visits. Blood and urine collection and liver function tests will occur at most study visits. For females, a pregnancy test will occur at screening and study entry.

RAL and DRV were provided by the study. RTV was not provided by the study.

Tipo de estudio

Intervencionista

Inscripción (Actual)

113

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35294
        • AlabamaTherapeutics CRS
    • California
      • Palo Alto, California, Estados Unidos, 94304
        • Stanford CRS
      • San Diego, California, Estados Unidos, 92103
        • Ucsd, Avrc Crs
      • San Francisco, California, Estados Unidos, 94110
        • Ucsf Aids Crs
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80045
        • University of Colorado Hospital CRS
    • District of Columbia
      • Washington, District of Columbia, Estados Unidos, 20007
        • Georgetown University CRS
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60611
        • Northwestern University CRS
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02115
        • Beth Israel Deaconess Med Center
      • Boston, Massachusetts, Estados Unidos, 02115
        • Brigham and Women's Hosp. ACTG CRS
    • Missouri
      • Saint Louis, Missouri, Estados Unidos, 63110
        • Washington U CRS
    • New York
      • Rochester, New York, Estados Unidos, 14604
        • AIDS Community Health Ctr. ACTG CRS
    • North Carolina
      • Chapel Hill, North Carolina, Estados Unidos, 27599
        • Unc Aids Crs
      • Durham, North Carolina, Estados Unidos, 27710
        • Duke Univ. Med. Ctr. Adult CRS
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45267-0405
        • Univ. of Cincinnati CRS
      • Cleveland, Ohio, Estados Unidos, 44106
        • Case CRS
      • Cleveland, Ohio, Estados Unidos, 44109
        • MetroHealth CRS
      • Columbus, Ohio, Estados Unidos, 43210
        • The Ohio State Univ. AIDS CRS
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
        • Hosp. of the Univ. of Pennsylvania CRS
      • Pittsburgh, Pennsylvania, Estados Unidos, 15213
        • University of Pittsburgh CTU
    • Rhode Island
      • Providence, Rhode Island, Estados Unidos, 02906
        • The Miriam Hospital
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37203
        • Vanderbilt Therapeutics CRS
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Houston AIDS Research Team

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • HIV-1-infected
  • Plasma HIV-1 RNA of at least 5,000 copies/mL within 90 days prior to study entry
  • HIV genotype (for reverse transcriptase and protease) performed at any time prior to study entry. More information on this criterion can be found in the protocol.
  • ARV drug-naive. More information on this criterion can be found in the protocol.
  • Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry
  • Agree to use one form of medically-accepted contraceptive throughout the study and for 60 days after stopping study treatment. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to study. More information on this criterion can be found in the protocol.
  • Screening HIV genotype obtained any time prior to study entry with more than one DRV resistance-associated mutation [RAM] (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76V alone
  • Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S
  • Severe renal insufficiency requiring hemodialysis or peritoneal dialysis
  • Treatment with immunomodulators within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • Current medications that are prohibited with any study medications. More information on this criterion can be found in the protocol.
  • Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion.
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study.
  • Certain abnormal laboratory results. More information on this criterion can be found in the protocol.
  • Pregnant or breastfeeding

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: RAL + DRV/RTV
Raltegravir (400 mg BID) plus Darunavir/Ritonavir (800 mg/100 mg QD) for 52 weeks
Droga: Raltegravir
400 mg tablet taken orally twice daily
Otros nombres:
  • RAL
Droga: Darunavir/Ritonavir
800 mg Darunavir/100 mg Ritonavir tablet taken orally once daily
Otros nombres:
  • DRV/RTV

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24
Periodo de tiempo: From start of study treatment to week 24
Virologic failure is defined as: at week 12, confirmed plasma HIV-1 RNA >= 1000 copies/ml or confirmed rebound from the week 4 value by >0.5 log10 copies/ml (for subjects with week 4 value <= 50 copies/ml, confirmed rebound to >50 copies/ml); at week 24 or later, confirmed value > 50 copies/ml. Viral load confirmation was scheduled 7-35 days after initial virologic failure. The proportion was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
From start of study treatment to week 24

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24
Periodo de tiempo: From start of study treatment to Week 24
The proportion of participants with virologic failure (see primary outcome measure for definition) and/or premature treatment discontinuation/modification and/or death was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
From start of study treatment to Week 24
Change in Plasma HIV-1 RNA From Baseline to Week 1
Periodo de tiempo: Baseline and week 1
Results report the week 1 change from baseline (week 1 - baseline) in HIV-1 RNA. Baseline HIV-1 RNA was computed as the mean of the log10 HIV-1 RNA values at pre-entry and study entry.
Baseline and week 1
Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24
Periodo de tiempo: From start of study treatment to week 24
Results report the percentage of participants with plasma HIV-1 RNA < 50 copies/ml or <200 copies/ml at week 24.
From start of study treatment to week 24
Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48
Periodo de tiempo: From start of study treatment to week 48
Results report the percentage of participants with plasma HIV-1 RNA <50 copies/ml or <200 copies/ml at week 48.
From start of study treatment to week 48
Proportion of Participants Who Experienced Signs/Symptoms or Laboratory Toxicities Grade 3 or Higher, or of Any Grade Which Led to a Permanent Change or Discontinuation of Study Treatment
Periodo de tiempo: From start of study treatment to week 52
Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System. Results report the percentage of participants who had grade 3 or higher events, or events of any grade which led to a permanent change or discontinuation of study treatment, which occurred any time from start of treatment to end of treatment.
From start of study treatment to week 52
Number of Participants With Pretreatment Drug Resistance
Periodo de tiempo: At screening
Results report the number of participants who had resistance to non-nucleoside reverse transciptase inhibitors (NNRTI), nucleoside reverse transciptase inhibitors (NRTI) and protease inbitors (PI) based on genotypic resistance testing done prior to participant's entry into the study. Participants are classified into one (and only one category) based on the maximum number of drug class resistance seen for the participant.
At screening
Number of Participants With Integrase Drug Resistance at Virologic Failure
Periodo de tiempo: From 12 weeks after starting study treatment to week 52
Results report the number of participants who had integrase resistance mutation(s) detected at the time of virologic failure.
From 12 weeks after starting study treatment to week 52
Number of Participants With Protease Drug Resistance at Virologic Failure
Periodo de tiempo: From 12 weeks after starting study treatment to week 52
Results report the number of participants who had protease resistance mutation(s) detected at the time of virologic failure.
From 12 weeks after starting study treatment to week 52
Number of Participants With Perfect Overall Adherence by Self Report
Periodo de tiempo: From one week after starting study treatment to week 52
At each study visit, adherence was measured in terms of the number of missed doses each participant had over a 4-day recall for each drug. Adherence for all study visit weeks were combined for an overall measure of adherence. Participants who had zero missed doses on all weeks in all drugs while on study were classified as having an overall "perfect" adherence.
From one week after starting study treatment to week 52
Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24
Periodo de tiempo: From start of study treatment through week 24
Results report the week 24 change from week 0 (week 24 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
From start of study treatment through week 24
Change in Fasting Low-density Lipoprotein at Week 24
Periodo de tiempo: From start of study treatment through week 24
Results report the week 24 change from week 0 (week 24 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.
From start of study treatment through week 24
Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48
Periodo de tiempo: From start of study treatment through week 48
Results report the week 48 change from week 0 (week 48 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
From start of study treatment through week 48
Change in Fasting Low-density Lipoprotein at Week 48
Periodo de tiempo: From start of study treatment through week 48
Results report the week 48 change from week 0 (week 48 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.
From start of study treatment through week 48
Change in CD4 Count at Week 48
Periodo de tiempo: From start of study treatment through week 48
Results report the week 48 change from baseline (week 48 - baseline) in CD4 count. Baseline CD4 count was computed as the mean of CD4 count values at pre-entry and study entry.
From start of study treatment through week 48
Plasma Trough Concentration of Raltegravir
Periodo de tiempo: From start of study treatment to week 52
Plasma trough concentrations (ng/ml) of Raltegravir (RAL) below the detection limit (10 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 9-15 hours after the last RAL dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
From start of study treatment to week 52
Plasma Trough Concentration of Darunavir
Periodo de tiempo: From start of study treatment to week 52
Plasma trough concentrations (ng/ml) of Darunavir (DRV) below the detection limit (50 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 20-28 hours after the last DRV dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
From start of study treatment to week 52

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

AIDS Clinical Trials Group

Colaboradores

National Institute of Allergy and Infectious Diseases (NIAID)

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de abril de 2009

Finalización primaria (Actual)

1 de febrero de 2010

Finalización del estudio (Actual)

1 de septiembre de 2010

Fechas de registro del estudio

Enviado por primera vez

26 de enero de 2009

Primero enviado que cumplió con los criterios de control de calidad

27 de enero de 2009

Publicado por primera vez (Estimar)

28 de enero de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de noviembre de 2018

Última actualización enviada que cumplió con los criterios de control de calidad

11 de octubre de 2018

Última verificación

1 de octubre de 2018

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • ACTG A5262
  • 1U01AI068636 (Subvención/contrato del NIH de EE. UU.)

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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